Induction of Plasmodium falciparum Transmission-Blocking Antibodies in Nonhuman Primates by a Combination of DNA and Protein Immunizations

Cevayir Coban, Mario T. Philipp, Jeanette E. Purcell, David B. Keistr, Mobolaji Okulate, Dale S. Martin, Nirbhay Kumar

Research output: Contribution to journalArticle

Abstract

Malaria transmission-blocking vaccination can effectively reduce and/or eliminate transmission of parasites from the human host to the mosquito vector. The immunity achieved by inducing an antibody response to surface antigens of male and female gametes and parasite stages in the mosquito. Our laboratory has developed DNA vaccine constructs, based on Pfs25 (a Plasmodium falciparum surface protein of 25 kDa), that induce a transmission-blocking immune response in mice (C. A. Lobo, R. Dhar, and N. Kumar, Infect. Immun. 67:1688-1693, 1999). To evaluate the safety, immunogenicity, and efficacy of the Pfs25 DNA vaccine in non-human primates, we immunized rhesus macaques (Macaca mulatta) with a DNA vaccine plasmid encoding Pfs25 or a Pfg27-Pfs25 hybrid or with the plasmid (empty plasmid) alone. Immunization with four doses of these DNA vaccine constructs elicited antibody titers that were high but nonetheless unable to reduce the parasite's infectivity in membrane feeding assays. Further boosting of the antibody response with recombinant Pfs25 formulated in Montanide ISA-720 increased antibody titers (30-fold) and significantly blocked transmission of P. falciparum gametocytes to Anopheles mosquitoes (∼90% reduction in oocyst numbers in the midgut). Our data show that a DNA prime-protein boost regimen holds promise for achieving transmission-blocking immunity in areas where malaria is endemic and could be effective in eradicating malaria in isolated areas whre the level of malaria endemicity is low.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalInfection and Immunity
Volume72
Issue number1
DOIs
StatePublished - Jan 2004

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Blocking Antibodies
Plasmodium falciparum
Primates
Immunization
DNA Vaccines
Membrane Proteins
Malaria
DNA
Parasites
Proteins
Plasmids
Culicidae
Macaca mulatta
Antibody Formation
Immunity
Anopheles
Oocysts
Antibodies
Surface Antigens
Germ Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Induction of Plasmodium falciparum Transmission-Blocking Antibodies in Nonhuman Primates by a Combination of DNA and Protein Immunizations. / Coban, Cevayir; Philipp, Mario T.; Purcell, Jeanette E.; Keistr, David B.; Okulate, Mobolaji; Martin, Dale S.; Kumar, Nirbhay.

In: Infection and Immunity, Vol. 72, No. 1, 01.2004, p. 253-259.

Research output: Contribution to journalArticle

Coban, Cevayir ; Philipp, Mario T. ; Purcell, Jeanette E. ; Keistr, David B. ; Okulate, Mobolaji ; Martin, Dale S. ; Kumar, Nirbhay. / Induction of Plasmodium falciparum Transmission-Blocking Antibodies in Nonhuman Primates by a Combination of DNA and Protein Immunizations. In: Infection and Immunity. 2004 ; Vol. 72, No. 1. pp. 253-259.
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